simeprevir 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
Hepatitis Virus C (HVC) protease inhibitors 4812 923604-59-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • olysio
  • TMC-435
  • TMC435350
  • simeprevir
  • simeprevir sodium
Oral HCV-PROTEASE INHIBITOR effective against hepatitis C virus (HCV) serine protease NS3/4A. It is used in the treatment of chronic hepatitis C (Antivirals) genotype 1 infection in adults with compensated liver disease, including CIRRHOSIS.
  • Molecular weight: 749.94
  • Formula: C38H47N5O7S2
  • CLOGP: 5.45
  • LIPINSKI: 3
  • HAC: 12
  • HDO: 2
  • TPSA: 156.89
  • ALOGS: -5.39
  • ROTB: 7
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.15 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.218 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 23.442 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 5 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 4.656 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.240 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.480 % High 1
herg hERG pIC50 4.752 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 4.457 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 25.351 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.290 % High 1
kinase-safety-class ACVR2B,EIF2AK3,GRK2,MAPK10,PDK1,PDK2,PDK4,PRKDC 8
kinase-selectivity-class PDK1 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 12.417 High 1
mh-clint Mouse hepatocyte intrinsic clearance 6.471 High 1
mppb Mouse plasma protein binding (% unbound) 0.210 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 104.713 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.420 % High 1
rh-clint Rat hepatocyte intrinsic clearance 9.750 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 1.460 % High 1
rppb Rat plasma protein binding (% unbound) 0.250 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 21.827 uM High 1

Approvals:

DateAgencyCompanyOrphan
May 14, 2014 EMA
Nov. 22, 2013 FDA JANSSEN PRODS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 841.74 40.48 301 4422 136668 90487056
Anaemia 640.02 40.48 326 4397 352476 90271248
White blood cell count decreased 507.24 40.48 221 4502 166888 90456836
Blood bilirubin increased 416.85 40.48 134 4589 43336 90580388
Neutrophil count decreased 291.32 40.48 117 4606 71415 90552309
Haemoglobin decreased 255.03 40.48 137 4586 161819 90461905
Hyperbilirubinaemia 175.39 40.48 53 4670 13883 90609841
Haemolytic anaemia 162.43 40.48 48 4675 11649 90612075
Hepatitis C 123.08 40.48 33 4690 5627 90618097
Hepatocellular carcinoma 118.01 40.48 27 4696 2401 90621323
Pruritus 96.36 40.48 129 4594 541396 90082328
Pyrexia 94.90 40.48 142 4581 660343 89963381
Photosensitivity reaction 93.10 40.48 35 4688 17772 90605952
Off label use 71.06 40.48 168 4555 1102084 89521640
Hepatic failure 52.36 40.48 30 4693 39698 90584026
Remission not achieved 50.65 40.48 9 4714 220 90623504
Jaundice 49.51 40.48 27 4696 32490 90591234
Hepatic function abnormal 48.11 40.48 30 4693 46258 90577466
Hepatic encephalopathy 44 40.48 19 4704 13753 90609971
Sunburn 43.55 40.48 13 4710 3254 90620470
Decreased appetite 42.83 40.48 73 4650 376467 90247257

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 563.01 29.23 299 5304 138282 42477450
White blood cell count decreased 407.49 29.23 224 5379 110172 42505560
Blood bilirubin increased 371.90 29.23 156 5447 42096 42573636
Anaemia 321.83 29.23 276 5327 280002 42335730
Hepatitis C 316.79 29.23 96 5507 10037 42605695
Hepatocellular carcinoma 274.92 29.23 82 5521 8112 42607620
Hyperbilirubinaemia 173.82 29.23 74 5529 20561 42595171
Haemoglobin decreased 162.21 29.23 136 5467 132335 42483397
Neutrophil count decreased 142.73 29.23 94 5509 63321 42552411
Photosensitivity reaction 142.64 29.23 56 5547 12646 42603086
Off label use 136.24 29.23 273 5330 638062 41977670
Jaundice 81.92 29.23 53 5550 34536 42581196
Remission not achieved 70.34 29.23 13 5590 150 42615582
Drug ineffective 69.65 29.23 210 5393 629987 41985745
Haemolytic anaemia 62.67 29.23 31 5572 12096 42603636
Pruritus 60.52 29.23 97 5506 188674 42427058
Sunburn 53.23 29.23 17 5586 2098 42613634
Hepatic failure 52.44 29.23 42 5561 38058 42577674
Genotype drug resistance test positive 48.93 29.23 14 5589 1190 42614542
Pyrexia 48.70 29.23 137 5466 393905 42221827
Hepatitis C RNA increased 45.21 29.23 10 5593 296 42615436
Treatment failure 45.00 29.23 48 5555 62576 42553156
Viral load increased 43.68 29.23 16 5587 2981 42612751
Hepatic encephalopathy 43.39 29.23 27 5576 16415 42599317
Ascites 41.71 29.23 44 5559 56634 42559098
Bilirubin conjugated increased 40.50 29.23 16 5587 3661 42612071
Thought blocking 39.97 29.23 8 5595 144 42615588
Choroiditis 34.39 29.23 11 5592 1364 42614368
Hyperuricaemia 34.14 29.23 19 5584 9405 42606327
Rash 33.81 29.23 96 5507 276858 42338874

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Platelet count decreased 1473.00 31.70 599 9034 229844 110349822
White blood cell count decreased 962.33 31.70 444 9189 228946 110350720
Anaemia 944.97 31.70 585 9048 546501 110033165
Blood bilirubin increased 749.08 31.70 272 9361 75700 110503966
Hepatitis C 440.72 31.70 119 9514 12454 110567212
Neutrophil count decreased 431.03 31.70 210 9423 120731 110458935
Haemoglobin decreased 428.40 31.70 267 9366 248460 110331206
Hepatocellular carcinoma 400.85 31.70 105 9528 9775 110569891
Hyperbilirubinaemia 332.35 31.70 118 9515 30553 110549113
Haemolytic anaemia 220.91 31.70 79 9554 20841 110558825
Photosensitivity reaction 149.94 31.70 63 9570 25526 110554140
Pyrexia 148.39 31.70 273 9360 897992 109681674
Pruritus 142.06 31.70 211 9422 581349 109998317
Jaundice 128.48 31.70 74 9559 59162 110520504
Remission not achieved 107.71 31.70 21 9612 506 110579160
Hepatic failure 100.99 31.70 67 9566 68672 110510994
Hepatic encephalopathy 74.06 31.70 40 9593 28216 110551450
Hepatitis C RNA increased 68.69 31.70 14 9619 425 110579241
Bilirubin conjugated increased 67.54 31.70 24 9609 6200 110573466
Ascites 62.54 31.70 57 9576 92751 110486915
Hyperuricaemia 60.01 31.70 28 9605 14503 110565163
Sunburn 58.85 31.70 20 9613 4528 110575138
Rash 57.36 31.70 179 9454 820785 109758881
Aspartate aminotransferase increased 57.10 31.70 70 9563 159866 110419800
Pain 56.75 31.70 8 9625 954947 109624719
Decreased appetite 53.69 31.70 124 9509 475722 110103944
Off label use 53.27 31.70 264 9369 1499921 109079745
Hepatorenal syndrome 50.92 31.70 18 9615 4579 110575087
Red blood cell count decreased 49.39 31.70 43 9590 65880 110513786
Hepatic function abnormal 49.05 31.70 49 9584 89246 110490420
Malaise 48.26 31.70 148 9485 671671 109907995
Insomnia 44.01 31.70 97 9536 360493 110219173
Alanine aminotransferase increased 43.63 31.70 66 9567 183707 110395959
Viral load increased 40.33 31.70 14 9619 3376 110576290
Thought blocking 38.69 31.70 8 9625 261 110579405
Choroiditis 37.10 31.70 11 9622 1604 110578062
Injection site pruritus 33.57 31.70 31 9602 51227 110528439
Injection site dermatitis 32.62 31.70 5 9628 26 110579640

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC J05AP05 ANTIINFECTIVES FOR SYSTEMIC USE
ANTIVIRALS FOR SYSTEMIC USE
DIRECT ACTING ANTIVIRALS
Antivirals for treatment of HCV infections
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000998 Antiviral Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D011480 Protease Inhibitors
FDA MoA N0000182138 Cytochrome P450 1A2 Inhibitors
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000182638 HCV NS3/4A Protease Inhibitors
FDA EPC N0000182639 Hepatitis C Virus NS3/4A Protease Inhibitor
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190107 Organic Anion Transporting Polypeptide 1B1 Inhibitors
FDA MoA N0000190108 Organic Anion Transporting Polypeptide 1B3 Inhibitors
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
FDA MoA N0000193845 Bile Salt Export Pump Inhibitors
FDA MoA N0000193960 Multidrug Resistance-Associated Protein 2 Inhibitors
FDA MoA N0000193965 Sodium Taurocholate Co-transporting Polypeptide Inhibitors
CHEBI has role CHEBI:22587 antiviral agent

Related Drugs by ATC class:

J05AP Antivirals for treatment of HCV infections 18 drugs
asunaprevirbeclabuvirboceprevirdaclatasvirdasabuvirelbasvirglecaprevirgrazoprevirledipasvirombitasvirparitaprevirpibrentasvir show all 18 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Chronic hepatitis C indication 128302006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.35 acidic
pKa2 6.66 Basic
pKa3 3.5 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8349869 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8741926 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8754106 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9040562 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9353103 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9623022 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 9856265 July 28, 2026 METHOD OF TREATING HEPATITIS C
EQ 150MG BASE OLYSIO JANSSEN PRODS N205123 Nov. 22, 2013 DISCN CAPSULE ORAL 8148399 Sept. 5, 2029 METHOD OF TREATING HEPATITIS C

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Cathepsin S Enzyme IC50 6.10 CHEMBL
Hepatitis C virus serine protease, NS3/NS4A Enzyme INHIBITOR Ki 9.30 CHEMBL CHEMBL
Genome polyprotein Polyprotein INHIBITOR Ki 9.44 SCIENTIFIC LITERATURE DRUG LABEL
Polyprotein Polyprotein INHIBITOR Ki 9.44 IUPHAR
NS3 protease Enzyme Ki 9.40 CHEMBL
Genome polyprotein Polyprotein Ki 9.30 CHEMBL
Replicase polyprotein 1ab Enzyme IC50 8.61 CHEMBL
Nonstructural protein NS3-4A Enzyme Ki 9.44 CHEMBL

External reference:

IDSource
D10081 KEGG_DRUG
4032900 VANDF
30B PDB_CHEM_ID
CHEMBL501849 ChEMBL_ID
CHEMBL3137358 ChEMBL_ID
7367 IUPHAR_LIGAND_ID
1241946-89-3 SECONDARY_CAS_RN
DB06290 DRUGBANK_ID
9WS5RD66HZ UNII
1482790 RXNORM
207569 MMSL
29896 MMSL
d08182 MMSL
015309 NDDF
015310 NDDF
708823009 SNOMEDCT_US
714167009 SNOMEDCT_US
C2605855 UMLSCUI
D000069616 MESH_DESCRIPTOR_UI
CHEBI:134743 CHEBI
9432 INN_ID
24873435 PUBCHEM_CID

Pharmaceutical products:

None